US6461632B1 - Hardenable ceramic hydraulic cement - Google Patents

Hardenable ceramic hydraulic cement Download PDF

Info

Publication number
US6461632B1
US6461632B1 US09/836,267 US83626701A US6461632B1 US 6461632 B1 US6461632 B1 US 6461632B1 US 83626701 A US83626701 A US 83626701A US 6461632 B1 US6461632 B1 US 6461632B1
Authority
US
United States
Prior art keywords
component
composition
calcium
acid
silicate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US09/836,267
Inventor
Sylwester Gogolewski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synthes USA LLC
Original Assignee
Synthes USA LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Synthes USA LLC filed Critical Synthes USA LLC
Assigned to SYNTHES (U.S.A.) reassignment SYNTHES (U.S.A.) ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GOGOLEWSKI, SYLWESTER
Application granted granted Critical
Publication of US6461632B1 publication Critical patent/US6461632B1/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/428—Vitamins, e.g. tocopherol, riboflavin

Definitions

  • This invention is directed to a method for delivering a drug via a hardenable ceramic hydraulic cement composition, implanted in an animal or human, that both hardens and dissolves or degrades in situ after time to release a therapeutically effective amount of the drug into a locally targeted area.
  • the invention further relates to the cement composition obtainable according to the method described, including a first component of at least one sodium or calcium salt of inorganic and organic acids, a second component of at least one alkaline, and optionally third and fourth components including an organic carboxylic acid and pure water, respectively.
  • Ceramic cements which harden in situ can be used for various applications. Such cements may be applied to reinforce porotic bones, to enhance fixation of fractures of porotic bones, to fill bone defects or to release bone growth factors.
  • the invention as claimed aims at solving both of the above described problems.
  • the invention relates to a ceramic hydraulic cement composition that includes a first component including at least one of a calcium or sodium salt of an inorganic and/or organic acid and a second component including an alkaline component.
  • the invention also related to a method of delivering the composition which includes providing a first component including at least one of a calcium or sodium salt of an inorganic and/or organic acid; providing a second component including an alkaline component; mixing the first and second components to form a ceramic hydraulic cement composition; and implanting a therapeutically effective amount of the composition into an animal or human, preferably human.
  • the composition hardens in situ and degrades in situ after a period of time to release a drug to a locally targeted area, preferably a bone defect.
  • the composition preferably degrades within 10 hours to 4 months, preferably within 10 hours to 30 days.
  • the calcium or sodium salt can include carbonic acid, phosphoric acid, or glycerophosphoric acid, or mixtures thereof.
  • the salt includes at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.
  • the first component can further include a therapeutically active agent.
  • the second component preferably includes sodium silicate or calcium silicate and is preferably present in the composition in an amount from 0.01 to 10 weight percent. In one embodiment, the second component also includes water.
  • the composition further includes a third component, preferably an organic carboxyclic acid, and more preferably at least one of ascorbic acid, citric acid, or tartaric acid.
  • a third component preferably an organic carboxyclic acid, and more preferably at least one of ascorbic acid, citric acid, or tartaric acid.
  • the composition includes an osteogenic agent., preferably at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.
  • the present invention provides a method for delivering a composition by implanting a hardenable ceramic hydraulic cement into a body, as defined in the claims.
  • the main advantage of the invention is the relatively short dissolving time of the hardened implanted cement compared to the above mentioned prior art cements which allows for faster delivery of drugs, in particular of osteogenic drugs.
  • a further component C which is an organic carboxylic acid
  • the organic carboxylic acid may be chosen from the group of ascorbic acid, citric acid or tartaric acid and has the function of neutralizing the alkaline components (sodium or calcium silicate) of the cement. Further advantages are the better compatibility with the environment and the faculty to complex calcium ions from the body fluids more easily and to deposit in the bone defect treated with the cement.
  • the use of ascorbic acid, in particular, further contributes to the formation of collagen in the bone defect treated with the cement.
  • Component A may preferably comprise calcium and/or sodium salts of carbonic acid, phosphoric acid or glycerophosphoric acid which are highly biocompatible, in particular if selected from the group of hydroxyapatite (HA), tricalcium phosphate (TCP), calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate or calcium glycerophosphate.
  • HA hydroxyapatite
  • TCP tricalcium phosphate
  • calcium carbonate calcium hydrogen phosphate
  • disodium hydrogen phosphate calcium glycerophosphate
  • water is incorporated in component B prior to mixing in order to obtain a shorter mixing time.
  • the concentration of the aqueous solution of sodium or calcium silicate of component B is in the range of 0.01% to 10.00% which facilitates preparation of the cement and thus contributes in controlling the acidity thereof.
  • the drugs added to the cement are chosen from the group of: osteogenic drugs, tissue growth factors (TGF-beta), osteocalcines, calcium binding proteins (GLA), bone morphogenetic proteins (BMP), antimicrobial drugs or vitamins.
  • the concentration is specific for the particular application and drug used.
  • HA hydroxyapatite
  • ascorbic acid 3 parts by weight of hydroxyapatite (HA) and 1 part by weight of ascorbic acid were mixed with 2 parts by weight of water and 0.1 parts by weight of sodium silicate. The mixture set within 10 to 20 minutes, and disintegrated when placed in water within 40 hours.
  • TCP tricalcium phosphate
  • ascorbic acid 3 parts by weight of tricalcium phosphate (TCP) and 1 part by weight of ascorbic acid were mixed with 2 parts by weight of water and 0.1 parts by weight of sodium silicate. The mixture set within 10 to 20 minutes, and disintegrated when placed in water within 30 hours.
  • HA hydroxyapatite
  • ascorbic acid 3 parts by weight of hydroxyapatite (HA) and 1 part by weight of ascorbic acid were mixed with 1 part by weight of water and 0.1 part by weight of calcium silicate. The mixture set within 15 minutes, and disintegrated when placed in water within 50 hours.
  • TCP tricalcium phosphate
  • ascorbic acid 1 part by weight of ascorbic acid
  • the mixture set within 15 minutes, and disintegrated when placed in water within 12 hours.
  • HA hydroxyapatite
  • TCP tricalcium phosphate
  • HA hydroxyapatite
  • TCP tricalcium phosphate
  • TCP tricalcium phosphate
  • Container X contained 10 parts by weight of calcium carbonate.
  • Container Y contained 2 parts by weight of ascorbic acid.
  • Container Z contained sodium silicate dissolved in water (glass water of the density in the range of 1.3 to 1.4 g/ml.
  • the liquid in container Z was put into contact with the powder of container X and subsequently the liquid in container Y was added. The resulting paste was mixed either by hand with a spatula or mechanically in mixing bowl.
  • the hardened cements showed a tensile strength in the range of 0.6 to 5.0 MPa; most of them in the range of 1 to 3 MPa.
  • the hardened cement mixtures according to the invention dissolve when placed in water within 10 hours to 4 months.
  • the short dissolution times from 10 hours to 30 days are preferably when cements are used for local delivery of osteogenic drugs (e.g., growth factors).
  • Salts used for preparation of cements should be of non-toxic nature. Acidity (pH-value) of the cements can be adjusted by changing the composition.
  • Glass water contains either sodium compounds in a form as expressed in Na 2 O between 6 to 1% or silica compounds as expressed in SiO 2 from 10 to 50%.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Curing Cements, Concrete, And Artificial Stone (AREA)
  • Ceramic Products (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

A method for delivering a therapeutically effective drug via a hardenable ceramic hydraulic cement composition including a first component of at least one sodium or calcium salts of inorganic and organic acids, a second component of at least one alkaline, and optionally third and fourth components including an organic carboxylic acid and pure water, respectively, wherein the cement composition is implanted in an animal or human body, hardens, and then degrades in situ after time to releases a amount of the drug into a locally targeted area.

Description

CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation of International Application No. PCT/EP98/06595, filed Oct. 19, 1998, the disclosure of which is hereby incorporated herein by express reference thereto.
FIELD OF INVENTION
This invention is directed to a method for delivering a drug via a hardenable ceramic hydraulic cement composition, implanted in an animal or human, that both hardens and dissolves or degrades in situ after time to release a therapeutically effective amount of the drug into a locally targeted area. The invention further relates to the cement composition obtainable according to the method described, including a first component of at least one sodium or calcium salt of inorganic and organic acids, a second component of at least one alkaline, and optionally third and fourth components including an organic carboxylic acid and pure water, respectively.
BACKGROUND OF THE INVENTION
Ceramic cements which harden in situ can be used for various applications. Such cements may be applied to reinforce porotic bones, to enhance fixation of fractures of porotic bones, to fill bone defects or to release bone growth factors.
Recently, resorbable cements, consisting of β-tricalciumphosphate, monocalcium phosphate and so-called carbonized cements containing calcium carbonate, became known that set at body temperature. These known cements have the disadvantage of long resorption or dissolution times. While this property is indispensable when cements are used to enhance bone fracture fixation, it is undesirable when cements are applied as carriers for fast local delivery of drugs.
The invention as claimed aims at solving both of the above described problems.
SUMMARY OF THE INVENTION
The invention relates to a ceramic hydraulic cement composition that includes a first component including at least one of a calcium or sodium salt of an inorganic and/or organic acid and a second component including an alkaline component. The invention also related to a method of delivering the composition which includes providing a first component including at least one of a calcium or sodium salt of an inorganic and/or organic acid; providing a second component including an alkaline component; mixing the first and second components to form a ceramic hydraulic cement composition; and implanting a therapeutically effective amount of the composition into an animal or human, preferably human. The composition hardens in situ and degrades in situ after a period of time to release a drug to a locally targeted area, preferably a bone defect. The composition preferably degrades within 10 hours to 4 months, preferably within 10 hours to 30 days.
The calcium or sodium salt can include carbonic acid, phosphoric acid, or glycerophosphoric acid, or mixtures thereof. Preferably, wherein the salt includes at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate. The first component can further include a therapeutically active agent.
The second component preferably includes sodium silicate or calcium silicate and is preferably present in the composition in an amount from 0.01 to 10 weight percent. In one embodiment, the second component also includes water.
In another embodiment, the composition further includes a third component, preferably an organic carboxyclic acid, and more preferably at least one of ascorbic acid, citric acid, or tartaric acid.
In one embodiment, the composition includes an osteogenic agent., preferably at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides a method for delivering a composition by implanting a hardenable ceramic hydraulic cement into a body, as defined in the claims. The main advantage of the invention is the relatively short dissolving time of the hardened implanted cement compared to the above mentioned prior art cements which allows for faster delivery of drugs, in particular of osteogenic drugs.
In a preferred embodiment of the invention, a further component C, which is an organic carboxylic acid, is used. The organic carboxylic acid may be chosen from the group of ascorbic acid, citric acid or tartaric acid and has the function of neutralizing the alkaline components (sodium or calcium silicate) of the cement. Further advantages are the better compatibility with the environment and the faculty to complex calcium ions from the body fluids more easily and to deposit in the bone defect treated with the cement. The use of ascorbic acid, in particular, further contributes to the formation of collagen in the bone defect treated with the cement.
Component A may preferably comprise calcium and/or sodium salts of carbonic acid, phosphoric acid or glycerophosphoric acid which are highly biocompatible, in particular if selected from the group of hydroxyapatite (HA), tricalcium phosphate (TCP), calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate or calcium glycerophosphate.
In a preferred embodiment water is incorporated in component B prior to mixing in order to obtain a shorter mixing time.
In a more preferred embodiment, the concentration of the aqueous solution of sodium or calcium silicate of component B is in the range of 0.01% to 10.00% which facilitates preparation of the cement and thus contributes in controlling the acidity thereof.
In a further preferred embodiment, the drugs added to the cement are chosen from the group of: osteogenic drugs, tissue growth factors (TGF-beta), osteocalcines, calcium binding proteins (GLA), bone morphogenetic proteins (BMP), antimicrobial drugs or vitamins. The concentration is specific for the particular application and drug used.
EXAMPLES
The various features of novelty which characterize the invention are pointed out with particularity in the claims appended to and forming part of this disclosure. For better understanding of the invention, its operating advantages and specific objects attained by its use, the following non-limiting examples, which are merely illustrative of the preferred embodiments of the present invention, and are not to be construed as limiting the invention, are incorporated as reference.
Example 1
5 parts by weight of calcium glycerophosphate and 1.5 parts by weight of 0.001−% aqueous solution of sodium silicate were mixed together and place in a plastic cylindrical mold. The mixture set within 60 to 90 minutes, and disintegrated when placed in water within 7 hours.
Example 2
3 parts by weight of hydroxyapatite (HA) and 1 part by weight of ascorbic acid were mixed with 2 parts by weight of water and 0.1 parts by weight of sodium silicate. The mixture set within 10 to 20 minutes, and disintegrated when placed in water within 40 hours.
Example 3
3 parts by weight of tricalcium phosphate (TCP) and 1 part by weight of ascorbic acid were mixed with 2 parts by weight of water and 0.1 parts by weight of sodium silicate. The mixture set within 10 to 20 minutes, and disintegrated when placed in water within 30 hours.
Example 4
3 parts by weight of hydroxyapatite (HA) and 1 part by weight of ascorbic acid were mixed with 1 part by weight of water and 0.1 part by weight of calcium silicate. The mixture set within 15 minutes, and disintegrated when placed in water within 50 hours.
Example 5
3 parts by weight of tricalcium phosphate (TCP) and 1 part by weight of ascorbic acid were mixed with 1 part by weight of water and 0.1 part by weight of calcium silicate. The mixture set within 15 minutes, and disintegrated when placed in water within 12 hours.
Example 6
2 parts by weight of hydroxyapatite (HA) were mixed with I part by weight of an aqueous solution sodium silicate (glass water) and 0.2 part by weight of ascorbic acid. The paste was mixed for 5 minutes and the paste obtained was allowed to set for 5 hours. When placed in water or saline solution it dissolved within 12 hours.
Example 7
2 parts by weight of tricalcium phosphate (TCP) were mixed with 1 part by weight of an aqueous solution of sodium silicate (glass water) and 0.2 part by weight of ascorbic acid. The paste was mixed for 5 minutes and the paste obtained was allowed to set for 5 hours. When placed in water or saline solution it dissolved within 12 hours.
Example 8
2 parts by weight of hydroxyapatite (HA) were mixed with 1 part by weight of ascorbic acid and 0.1 part by weight of an aqueous solution of sodium silicate (glass water). The paste obtained set within 15 minutes and dissolved when placed in water within 40 days. Increasing the amount of ascorbic acid in the cement mixture decreases time required for the cement setting and extends the dissolution time in water.
Example 9
2 parts by weight of tricalcium phosphate (TCP) were mixed with 0.5 parts by weight of ascorbic acid and 0.1 part by weight of an aqueous solution of sodium silicate (glass water). The paste obtained set within 15 minutes and dissolved when placed in water within 40 days. Increasing the amount of ascorbic acid in the cement mixture decreases time required for the cement setting and extends the dissolution time in water.
Example 10
2 parts by weight of calcium carbonate were mixed with 1 part by weight of an aqueous solution of sodium silicate (glass water) and 1 part by weight of ascorbic acid. The cement set within 20 minutes and dissolved in water within 40 days.
Example 11
2 parts by weight of calcium carbonate were mixed with 1 part by weight of an aqueous solution of sodium silicate (glass water) and 0.5 parts by weight of ascorbic acid. The cement set within 20 minutes and dissolved in water within 30 days.
Example 12
3 parts by weight of tricalcium phosphate (TCP) were mixed with 3 parts by weight of calcium glycerol phosphate and 0.5 parts of ascorbic acid, 0.01 parts by weight of an aqueous solution of sodium silicate (glass water) and 1 part of water. The paste obtained set within 30 minutes. Disintegration time in water was from 10 days.
Example 13
4 parts by weight of calcium glycerophosphate, 0.01 part by weight of an aqueous solution of sodium silicate (glass water) and 0.05 part by weight 1 wt− % aqueous solution of ascorbic acid were mixed together with 1 part by weight of deionised water. The resulting paste set within 1 hour the paste disintegration.
Example 14
In this example the cement composition is stored in three separate containers X, Y and Z. Container X contained 10 parts by weight of calcium carbonate. Container Y contained 2 parts by weight of ascorbic acid. Container Z contained sodium silicate dissolved in water (glass water of the density in the range of 1.3 to 1.4 g/ml. For initiating the hardening process the liquid in container Z was put into contact with the powder of container X and subsequently the liquid in container Y was added. The resulting paste was mixed either by hand with a spatula or mechanically in mixing bowl.
Physical Properties of the Hardened Cements According to the Examples
The hardened cements showed a tensile strength in the range of 0.6 to 5.0 MPa; most of them in the range of 1 to 3 MPa.
Depending on the chemical composition, the hardened cement mixtures according to the invention dissolve when placed in water within 10 hours to 4 months. The short dissolution times from 10 hours to 30 days are preferably when cements are used for local delivery of osteogenic drugs (e.g., growth factors).
Salts used for preparation of cements should be of non-toxic nature. Acidity (pH-value) of the cements can be adjusted by changing the composition.
Glass water contains either sodium compounds in a form as expressed in Na2O between 6 to 1% or silica compounds as expressed in SiO2 from 10 to 50%.
While the foregoing description and drawings represent the preferred embodiments of the present invention, it will be obvious for those of ordinary skill in the art that various changes and modifications may be made therein without departing from the true spirit and scope of the present invention.

Claims (34)

What is claimed is:
1. A method of delivering a composition which comprises:
providing a first component comprising at least one of a calcium or sodium salt of an inorganic and/or organic acid;
providing a second component comprising sodium silicate or calcium silicate;
mixing the first and second components to form a ceramic hydraulic cement composition; and
implanting a therapeutically effective amount of the composition into an animal,
wherein the first component is different from the second component,
wherein the composition hardens in situ,
and wherein the composition degrades in situ over a period of time to release a drug to a locally targeted area.
2. The method of claim 1, wherein the inorganic and/or organic acid comprises carbonic acid, phosphoric acid, or glycerophosphoric acid.
3. The method of claim 2, wherein the calcium or sodium salt comprises at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.
4. The method of claim 1, wherein the first component further comprises a therapeutically active agent and the animal is human.
5. The method of claim 1, wherein the second component comprises an aqueous solution of sodium silicate or calcium silicate.
6. The method of claim 1, wherein the second component further comprises water.
7. The method of claim 6, wherein the amount of the sodium silicate or calcium silicate in the second component is from 0.01 to 10 weight percent.
8. The method of claim 1, wherein the composition further comprises a third component comprising an organic carboxylic acid.
9. The method of claim 8, wherein the third component comprises at east one of ascorbic acid, citric acid, or tartaric acid.
10. The method of claim 8, wherein the third component comprises ascorbic acid.
11. The method of claim 1, wherein the composition degrades in 10 hours to 4 months.
12. The method of claim 11, wherein the composition degrades in 10 hours to 30 days.
13. The method of claim 1, wherein the locally targeted area is a bone defect.
14. The method of claim 1, wherein the composition further comprises an osteogenic agent.
15. The method of claim 14, wherein the osteogenic agent comprises at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.
16. A ceramic hydraulic cement composition comprising:
a first component comprising at least one of a calcium or sodium salt of an inorganic and/or organic acid;
a second component comprising sodium silicate or calcium silicate; and
a third component comprising an organic carboxylic acid,
wherein the first component is different from the second component, and
wherein the composition degrades in the presence of water in 10 hours to 4 months.
17. The composition of claim 16, wherein the inorganic and/or organic acid comprises carbonic acid, phosphoric acid, or glycerophosphoric acid.
18. The composition of claim 17, wherein the calcium or sodium salt comprises at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.
19. The composition of claim 16, wherein the first component comprises therapeutically active agent and the animal is human.
20. The composition of claim 16, wherein the composition further comprises at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.
21. The composition of claim 16, wherein the composition degrades in water in 10 hours to 30 days.
22. The composition of claim 16, wherein the second component comprises an aqueous solution of sodium silicate or calcium silicate.
23. The composition of claim 16, wherein the second component further comprises water.
24. The composition of claim 23, wherein the amount of the sodium silicate or calcium silicate in the second component is from 0.01 to 10 weight percent.
25. The composition of claim 16, wherein the composition further comprises a fourth component comprising pure water.
26. The composition of claim 25, wherein the third component comprises at least one of ascorbic acid, citric acid, or tartaric acid.
27. A method of delivering a composition which comprises:
providing a first component comprising at least one of a calcium or sodium salt of an inorganic and/or organic acid;
providing a second component comprising sodium silicate or calcium silicate;
providing a third component comprising an organic carboxylic acid;
mixing the first, second, and third components to form a ceramic hydraulic cement composition; and
implanting a therapeutically effective amount of the composition into an human, wherein the first the component is different from the second component,
wherein the composition hardens in situ,
and wherein the composition degrades in situ over a period of time to release a drug to a locally targeted area.
28. The method of claim 27, wherein the inorganic and/or organic acid comprises carbonic acid, phosphoric acid, or glycerophosphoric acid.
29. The method of claim 28, wherein the calcium or sodium salt comprises at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.
30. The method of claim 8, wherein the first component further comprises a therapeutically active agent and the animal is human.
31. The method of claim 8, wherein the second component further comprises water, and wherein the amount of the sodium silicate or calcium silicate in the second component is from 0.01 to 10 weight percent.
32. The method of claim 8, wherein the third component comprises at least one of ascorbic acid, citric acid, or tartaric acid.
33. The method of claim 8, wherein the composition degrades in 10 hours to 4 months.
34. The method of claim 30, wherein the locally targeted area is a bone defect and wherein the therapeutically active agent comprises at least one osteogenic agent comprising growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.
US09/836,267 1998-10-19 2001-04-18 Hardenable ceramic hydraulic cement Expired - Fee Related US6461632B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP1998/006595 WO2000023123A1 (en) 1998-10-19 1998-10-19 Hardenable ceramic hydraulic cement

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/006595 Continuation WO2000023123A1 (en) 1998-10-19 1998-10-19 Hardenable ceramic hydraulic cement

Publications (1)

Publication Number Publication Date
US6461632B1 true US6461632B1 (en) 2002-10-08

Family

ID=8167098

Family Applications (1)

Application Number Title Priority Date Filing Date
US09/836,267 Expired - Fee Related US6461632B1 (en) 1998-10-19 2001-04-18 Hardenable ceramic hydraulic cement

Country Status (12)

Country Link
US (1) US6461632B1 (en)
EP (1) EP1123081B1 (en)
JP (1) JP2002527208A (en)
AT (1) ATE229350T1 (en)
AU (1) AU746591B2 (en)
CA (1) CA2346651A1 (en)
DE (1) DE69810165T2 (en)
DK (1) DK1123081T3 (en)
ES (1) ES2185227T3 (en)
HK (1) HK1039074B (en)
WO (1) WO2000023123A1 (en)
ZA (1) ZA996601B (en)

Cited By (89)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6719993B2 (en) 2000-04-28 2004-04-13 Skeletal Kinetics, Llc Calcium phosphate cements prepared from silicate solutions
US20040250730A1 (en) * 2003-06-12 2004-12-16 David Delaney Calcium phosphate cements prepared from silicate-phosphate solutions
US20050023171A1 (en) * 2003-07-28 2005-02-03 David Delaney Calcium phosphate cements comprising a water-soluble contrast agent
US20070282434A1 (en) * 2006-05-30 2007-12-06 Yunbing Wang Copolymer-bioceramic composite implantable medical devices
CN100391418C (en) * 2004-03-05 2008-06-04 中国科学院上海硅酸盐研究所 Bioactive composite cytoskeleton made of degradable porous polyester/calcium silicate, prepn. method and use thereof
WO2008148055A1 (en) * 2007-05-24 2008-12-04 Calera Corporation Hydraulic cements comprising carbonate compounds compositions
US20090074871A1 (en) * 2007-09-14 2009-03-19 Musculoskeletal Transplant Foundation Composition for filling bone defects
US7658880B2 (en) 2005-07-29 2010-02-09 Advanced Cardiovascular Systems, Inc. Polymeric stent polishing method and apparatus
US7662326B2 (en) 2004-09-10 2010-02-16 Advanced Cardiovascular Systems, Inc. Compositions containing fast-leaching plasticizers for improved performance of medical devices
US7699890B2 (en) 1997-04-15 2010-04-20 Advanced Cardiovascular Systems, Inc. Medicated porous metal prosthesis and a method of making the same
US7708548B2 (en) 2005-04-12 2010-05-04 Advanced Cardiovascular Systems, Inc. Molds for fabricating stents with profiles for gripping a balloon catheter
US20100119492A1 (en) * 2008-10-31 2010-05-13 Synthes Usa, Llc Method and device for activating stem cells
US7731890B2 (en) 2006-06-15 2010-06-08 Advanced Cardiovascular Systems, Inc. Methods of fabricating stents with enhanced fracture toughness
US7740791B2 (en) 2006-06-30 2010-06-22 Advanced Cardiovascular Systems, Inc. Method of fabricating a stent with features by blow molding
US7758881B2 (en) 2004-06-30 2010-07-20 Advanced Cardiovascular Systems, Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US7757543B2 (en) 2006-07-13 2010-07-20 Advanced Cardiovascular Systems, Inc. Radio frequency identification monitoring of stents
US7761968B2 (en) 2006-05-25 2010-07-27 Advanced Cardiovascular Systems, Inc. Method of crimping a polymeric stent
US7794776B1 (en) 2006-06-29 2010-09-14 Abbott Cardiovascular Systems Inc. Modification of polymer stents with radiation
US7794495B2 (en) 2006-07-17 2010-09-14 Advanced Cardiovascular Systems, Inc. Controlled degradation of stents
US7820191B2 (en) 2000-04-28 2010-10-26 Skeletal Kinetics, Llc Calcium phosphate cements prepared from silicate solutions
US7823263B2 (en) 2006-07-11 2010-11-02 Abbott Cardiovascular Systems Inc. Method of removing stent islands from a stent
US7829008B2 (en) 2007-05-30 2010-11-09 Abbott Cardiovascular Systems Inc. Fabricating a stent from a blow molded tube
US20100298124A1 (en) * 2007-08-03 2010-11-25 Errcive, Inc. Porous Bodies and Methods
US7842737B2 (en) 2006-09-29 2010-11-30 Abbott Cardiovascular Systems Inc. Polymer blend-bioceramic composite implantable medical devices
US7867547B2 (en) 2005-12-19 2011-01-11 Advanced Cardiovascular Systems, Inc. Selectively coating luminal surfaces of stents
US7875233B2 (en) 2004-09-30 2011-01-25 Advanced Cardiovascular Systems, Inc. Method of fabricating a biaxially oriented implantable medical device
US7886419B2 (en) 2006-07-18 2011-02-15 Advanced Cardiovascular Systems, Inc. Stent crimping apparatus and method
US7901452B2 (en) 2007-06-27 2011-03-08 Abbott Cardiovascular Systems Inc. Method to fabricate a stent having selected morphology to reduce restenosis
US7923022B2 (en) 2006-09-13 2011-04-12 Advanced Cardiovascular Systems, Inc. Degradable polymeric implantable medical devices with continuous phase and discrete phase
US7951194B2 (en) 2006-05-26 2011-05-31 Abbott Cardiovascular Sysetms Inc. Bioabsorbable stent with radiopaque coating
US7951185B1 (en) 2006-01-06 2011-05-31 Advanced Cardiovascular Systems, Inc. Delivery of a stent at an elevated temperature
US7955381B1 (en) 2007-06-29 2011-06-07 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical device with different types of bioceramic particles
US7959857B2 (en) 2007-06-01 2011-06-14 Abbott Cardiovascular Systems Inc. Radiation sterilization of medical devices
US7959940B2 (en) 2006-05-30 2011-06-14 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical devices
US7964210B2 (en) 2006-03-31 2011-06-21 Abbott Cardiovascular Systems Inc. Degradable polymeric implantable medical devices with a continuous phase and discrete phase
US7967998B2 (en) 2003-06-25 2011-06-28 Advanced Cardiocasvular Systems, Inc. Method of polishing implantable medical devices to lower thrombogenecity and increase mechanical stability
US7971333B2 (en) 2006-05-30 2011-07-05 Advanced Cardiovascular Systems, Inc. Manufacturing process for polymetric stents
US7989018B2 (en) 2001-09-17 2011-08-02 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US7998404B2 (en) 2006-07-13 2011-08-16 Advanced Cardiovascular Systems, Inc. Reduced temperature sterilization of stents
US8003156B2 (en) 2006-05-04 2011-08-23 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8017237B2 (en) 2006-06-23 2011-09-13 Abbott Cardiovascular Systems, Inc. Nanoshells on polymers
US8016879B2 (en) 2006-08-01 2011-09-13 Abbott Cardiovascular Systems Inc. Drug delivery after biodegradation of the stent scaffolding
US8034287B2 (en) 2006-06-01 2011-10-11 Abbott Cardiovascular Systems Inc. Radiation sterilization of medical devices
US8043553B1 (en) 2004-09-30 2011-10-25 Advanced Cardiovascular Systems, Inc. Controlled deformation of a polymer tube with a restraining surface in fabricating a medical article
US8048441B2 (en) 2007-06-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Nanobead releasing medical devices
US8048448B2 (en) 2006-06-15 2011-11-01 Abbott Cardiovascular Systems Inc. Nanoshells for drug delivery
US8099849B2 (en) 2006-12-13 2012-01-24 Abbott Cardiovascular Systems Inc. Optimizing fracture toughness of polymeric stent
US8128688B2 (en) 2006-06-27 2012-03-06 Abbott Cardiovascular Systems Inc. Carbon coating on an implantable device
US8173062B1 (en) 2004-09-30 2012-05-08 Advanced Cardiovascular Systems, Inc. Controlled deformation of a polymer tube in fabricating a medical article
US8172897B2 (en) 1997-04-15 2012-05-08 Advanced Cardiovascular Systems, Inc. Polymer and metal composite implantable medical devices
US8197879B2 (en) 2003-09-30 2012-06-12 Advanced Cardiovascular Systems, Inc. Method for selectively coating surfaces of a stent
US8202528B2 (en) 2007-06-05 2012-06-19 Abbott Cardiovascular Systems Inc. Implantable medical devices with elastomeric block copolymer coatings
US8241554B1 (en) 2004-06-29 2012-08-14 Advanced Cardiovascular Systems, Inc. Method of forming a stent pattern on a tube
US8262723B2 (en) 2007-04-09 2012-09-11 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from polymer blends with star-block copolymers
US8277743B1 (en) 2009-04-08 2012-10-02 Errcive, Inc. Substrate fabrication
US8278368B2 (en) 2004-11-16 2012-10-02 3M Innnovatve Properties Company Dental fillers, methods, compositions including a caseinate
US8293260B2 (en) 2007-06-05 2012-10-23 Abbott Cardiovascular Systems Inc. Elastomeric copolymer coatings containing poly (tetramethyl carbonate) for implantable medical devices
US8333000B2 (en) 2006-06-19 2012-12-18 Advanced Cardiovascular Systems, Inc. Methods for improving stent retention on a balloon catheter
US8343530B2 (en) 2006-05-30 2013-01-01 Abbott Cardiovascular Systems Inc. Polymer-and polymer blend-bioceramic composite implantable medical devices
US8359829B1 (en) 2009-06-25 2013-01-29 Ramberg Charles E Powertrain controls
US8425591B1 (en) 2007-06-11 2013-04-23 Abbott Cardiovascular Systems Inc. Methods of forming polymer-bioceramic composite medical devices with bioceramic particles
US8435550B2 (en) 2002-12-16 2013-05-07 Abbot Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8470014B2 (en) 2004-08-25 2013-06-25 Advanced Cardiovascular Systems, Inc. Stent-catheter assembly with a releasable connection for stent retention
US8486135B2 (en) 2006-06-01 2013-07-16 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from branched polymers
US8535372B1 (en) 2006-06-16 2013-09-17 Abbott Cardiovascular Systems Inc. Bioabsorbable stent with prohealing layer
US8568469B1 (en) 2004-06-28 2013-10-29 Advanced Cardiovascular Systems, Inc. Stent locking element and a method of securing a stent on a delivery system
US8603530B2 (en) 2006-06-14 2013-12-10 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8710114B2 (en) 2004-11-16 2014-04-29 3M Innovative Properties Company Dental fillers including a phosphorus containing surface treatment, and compositions and methods thereof
US8747878B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device by controlling crystalline structure
US8747879B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device to reduce chance of late inflammatory response
US8752268B2 (en) 2006-05-26 2014-06-17 Abbott Cardiovascular Systems Inc. Method of making stents with radiopaque markers
US8778256B1 (en) 2004-09-30 2014-07-15 Advanced Cardiovascular Systems, Inc. Deformation of a polymer tube in the fabrication of a medical article
US8790707B2 (en) 2008-12-11 2014-07-29 3M Innovative Properties Company Surface-treated calcium phosphate particles suitable for oral care and dental compositions
US8957126B2 (en) 2004-11-16 2015-02-17 3M Innovative Properties Company Dental compositions with calcium phosphorus releasing glass
US9072820B2 (en) 2006-06-26 2015-07-07 Advanced Cardiovascular Systems, Inc. Polymer composite stent with polymer particles
US9173733B1 (en) 2006-08-21 2015-11-03 Abbott Cardiovascular Systems Inc. Tracheobronchial implantable medical device and methods of use
US9198785B2 (en) 2010-01-30 2015-12-01 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds
US9248034B2 (en) 2005-08-23 2016-02-02 Advanced Cardiovascular Systems, Inc. Controlled disintegrating implantable medical devices
US9295570B2 (en) 2001-09-19 2016-03-29 Abbott Laboratories Vascular Enterprises Limited Cold-molding process for loading a stent onto a stent delivery system
US9532888B2 (en) 2006-01-04 2017-01-03 Abbott Cardiovascular Systems Inc. Stents with radiopaque markers
US9827119B2 (en) 2010-01-30 2017-11-28 Abbott Cardiovascular Systems Inc. Polymer scaffolds having a low crossing profile
US9833932B1 (en) 2010-06-30 2017-12-05 Charles E. Ramberg Layered structures
US9999527B2 (en) 2015-02-11 2018-06-19 Abbott Cardiovascular Systems Inc. Scaffolds having radiopaque markers
US10028851B2 (en) 1997-04-15 2018-07-24 Advanced Cardiovascular Systems, Inc. Coatings for controlling erosion of a substrate of an implantable medical device
US10137061B2 (en) * 2004-11-16 2018-11-27 3M Innovative Properties Company Dental fillers and compositions including phosphate salts
US10307274B2 (en) 2011-07-29 2019-06-04 Abbott Cardiovascular Systems Inc. Methods for uniform crimping and deployment of a polymer scaffold
US10531957B2 (en) 2015-05-21 2020-01-14 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
US10563153B2 (en) 2010-05-20 2020-02-18 Ecolab Usa Inc. Rheology modified low foaming liquid antimicrobial compositions and methods of use thereof
US10610387B2 (en) 2015-06-12 2020-04-07 Abbott Cardiovascular Systems Inc. Scaffolds having a radiopaque marker and methods for attaching a marker to a scaffold

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6730324B2 (en) 2001-04-20 2004-05-04 The University Of British Columbia Biofunctional hydroxyapatite coatings and microspheres for in-situ drug encapsulation
US20050123490A1 (en) * 2003-12-04 2005-06-09 Kazue Yamagishi Composition and method for prevention and treatment of dental caries
FR2869544B1 (en) * 2004-05-03 2006-07-21 Centre Nat Rech Scient Cnrse COMPOSITION FOR INJECTION CEMENT, USEFUL AS BONE SUBSTITUTE
EP1861341B1 (en) * 2005-03-25 2015-10-14 Innovative Bioceramix, Inc. Hydraulic cement compositions
US7553362B2 (en) * 2005-10-31 2009-06-30 Innovative Bioceramix, Inc. High strength biological cement composition and using the same
ES2387379T3 (en) * 2009-09-17 2012-09-21 Stryker Corporation Buffers to control the pH of bone morphogenetic proteins
CA3046522A1 (en) * 2016-12-09 2018-06-14 Northwestern University Bone-promoting thermoresponsive macromolecules

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4596574A (en) 1984-05-14 1986-06-24 The Regents Of The University Of California Biodegradable porous ceramic delivery system for bone morphogenetic protein
JPH03109077A (en) * 1989-09-21 1991-05-09 Lion Corp Biomaterial
US5082808A (en) * 1988-07-04 1992-01-21 Tdk Corporation Ceramic material and method for making
US5149368A (en) * 1991-01-10 1992-09-22 Liu Sung Tsuen Resorbable bioactive calcium phosphate cement
US5336264A (en) * 1988-04-20 1994-08-09 Norian Corporation Situ prepared calcium phosphate composition and method
US5648097A (en) * 1995-10-04 1997-07-15 Biotek, Inc. Calcium mineral-based microparticles and method for the production thereof
WO1998008773A1 (en) 1996-08-30 1998-03-05 Abonetics Limited Silicon-substituted apatites and process for the preparation thereof
WO1999017710A1 (en) 1997-10-07 1999-04-15 Dr. H.C. Robert Mathys Stiftung Hydraulic surgical cement
US6214048B1 (en) * 1992-02-10 2001-04-10 Matsumoto Dental College Bone substitute product and method of producing the same

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4596574A (en) 1984-05-14 1986-06-24 The Regents Of The University Of California Biodegradable porous ceramic delivery system for bone morphogenetic protein
US5336264A (en) * 1988-04-20 1994-08-09 Norian Corporation Situ prepared calcium phosphate composition and method
US5082808A (en) * 1988-07-04 1992-01-21 Tdk Corporation Ceramic material and method for making
JPH03109077A (en) * 1989-09-21 1991-05-09 Lion Corp Biomaterial
US5149368A (en) * 1991-01-10 1992-09-22 Liu Sung Tsuen Resorbable bioactive calcium phosphate cement
US6214048B1 (en) * 1992-02-10 2001-04-10 Matsumoto Dental College Bone substitute product and method of producing the same
US5648097A (en) * 1995-10-04 1997-07-15 Biotek, Inc. Calcium mineral-based microparticles and method for the production thereof
WO1998008773A1 (en) 1996-08-30 1998-03-05 Abonetics Limited Silicon-substituted apatites and process for the preparation thereof
WO1999017710A1 (en) 1997-10-07 1999-04-15 Dr. H.C. Robert Mathys Stiftung Hydraulic surgical cement

Cited By (145)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8007529B2 (en) 1997-04-15 2011-08-30 Advanced Cardiovascular Systems, Inc. Medicated porous metal prosthesis
US7699890B2 (en) 1997-04-15 2010-04-20 Advanced Cardiovascular Systems, Inc. Medicated porous metal prosthesis and a method of making the same
US8172897B2 (en) 1997-04-15 2012-05-08 Advanced Cardiovascular Systems, Inc. Polymer and metal composite implantable medical devices
US10028851B2 (en) 1997-04-15 2018-07-24 Advanced Cardiovascular Systems, Inc. Coatings for controlling erosion of a substrate of an implantable medical device
US6719993B2 (en) 2000-04-28 2004-04-13 Skeletal Kinetics, Llc Calcium phosphate cements prepared from silicate solutions
US7820191B2 (en) 2000-04-28 2010-10-26 Skeletal Kinetics, Llc Calcium phosphate cements prepared from silicate solutions
US7989018B2 (en) 2001-09-17 2011-08-02 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US9295570B2 (en) 2001-09-19 2016-03-29 Abbott Laboratories Vascular Enterprises Limited Cold-molding process for loading a stent onto a stent delivery system
US10166131B2 (en) 2001-09-19 2019-01-01 Abbott Laboratories Vascular Enterprises Limited Process for loading a stent onto a stent delivery system
US8435550B2 (en) 2002-12-16 2013-05-07 Abbot Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US20040250730A1 (en) * 2003-06-12 2004-12-16 David Delaney Calcium phosphate cements prepared from silicate-phosphate solutions
US7967998B2 (en) 2003-06-25 2011-06-28 Advanced Cardiocasvular Systems, Inc. Method of polishing implantable medical devices to lower thrombogenecity and increase mechanical stability
US7306786B2 (en) 2003-07-28 2007-12-11 Skeletal Kinetics, Llc Calcium phosphate cements comprising a water-soluble contrast agent
US20050023171A1 (en) * 2003-07-28 2005-02-03 David Delaney Calcium phosphate cements comprising a water-soluble contrast agent
US8197879B2 (en) 2003-09-30 2012-06-12 Advanced Cardiovascular Systems, Inc. Method for selectively coating surfaces of a stent
CN100391418C (en) * 2004-03-05 2008-06-04 中国科学院上海硅酸盐研究所 Bioactive composite cytoskeleton made of degradable porous polyester/calcium silicate, prepn. method and use thereof
US8568469B1 (en) 2004-06-28 2013-10-29 Advanced Cardiovascular Systems, Inc. Stent locking element and a method of securing a stent on a delivery system
US8241554B1 (en) 2004-06-29 2012-08-14 Advanced Cardiovascular Systems, Inc. Method of forming a stent pattern on a tube
US7758881B2 (en) 2004-06-30 2010-07-20 Advanced Cardiovascular Systems, Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8470014B2 (en) 2004-08-25 2013-06-25 Advanced Cardiovascular Systems, Inc. Stent-catheter assembly with a releasable connection for stent retention
US9283099B2 (en) 2004-08-25 2016-03-15 Advanced Cardiovascular Systems, Inc. Stent-catheter assembly with a releasable connection for stent retention
US7662326B2 (en) 2004-09-10 2010-02-16 Advanced Cardiovascular Systems, Inc. Compositions containing fast-leaching plasticizers for improved performance of medical devices
US7875233B2 (en) 2004-09-30 2011-01-25 Advanced Cardiovascular Systems, Inc. Method of fabricating a biaxially oriented implantable medical device
US8173062B1 (en) 2004-09-30 2012-05-08 Advanced Cardiovascular Systems, Inc. Controlled deformation of a polymer tube in fabricating a medical article
US8778256B1 (en) 2004-09-30 2014-07-15 Advanced Cardiovascular Systems, Inc. Deformation of a polymer tube in the fabrication of a medical article
US8043553B1 (en) 2004-09-30 2011-10-25 Advanced Cardiovascular Systems, Inc. Controlled deformation of a polymer tube with a restraining surface in fabricating a medical article
US9517186B2 (en) 2004-11-16 2016-12-13 3M Innovative Properties Company Dental compositions with calcium phosphorus releasing glass
US8450388B2 (en) 2004-11-16 2013-05-28 3M Innovative Properties Company Dental fillers, methods, compositions including a caseinate
US8957126B2 (en) 2004-11-16 2015-02-17 3M Innovative Properties Company Dental compositions with calcium phosphorus releasing glass
US8710114B2 (en) 2004-11-16 2014-04-29 3M Innovative Properties Company Dental fillers including a phosphorus containing surface treatment, and compositions and methods thereof
US20190091108A1 (en) * 2004-11-16 2019-03-28 3M Innovative Properties Company Dental fillers, methods, and compositions including a phosphate salt
US10137061B2 (en) * 2004-11-16 2018-11-27 3M Innovative Properties Company Dental fillers and compositions including phosphate salts
US9233054B2 (en) 2004-11-16 2016-01-12 3M Innovative Properties Company Dental fillers including a phosphorus-containing surface treatment, and compositions and methods thereof
US8278368B2 (en) 2004-11-16 2012-10-02 3M Innnovatve Properties Company Dental fillers, methods, compositions including a caseinate
US9414995B2 (en) 2004-11-16 2016-08-16 3M Innovative Properties Company Dental fillers including a phosphorus-containing surface treatment, and compositions and methods thereof
US7708548B2 (en) 2005-04-12 2010-05-04 Advanced Cardiovascular Systems, Inc. Molds for fabricating stents with profiles for gripping a balloon catheter
US7658880B2 (en) 2005-07-29 2010-02-09 Advanced Cardiovascular Systems, Inc. Polymeric stent polishing method and apparatus
US9248034B2 (en) 2005-08-23 2016-02-02 Advanced Cardiovascular Systems, Inc. Controlled disintegrating implantable medical devices
US7867547B2 (en) 2005-12-19 2011-01-11 Advanced Cardiovascular Systems, Inc. Selectively coating luminal surfaces of stents
US10070975B2 (en) 2006-01-04 2018-09-11 Abbott Cardiovascular Systems Inc. Stents with radiopaque markers
US9532888B2 (en) 2006-01-04 2017-01-03 Abbott Cardiovascular Systems Inc. Stents with radiopaque markers
US7951185B1 (en) 2006-01-06 2011-05-31 Advanced Cardiovascular Systems, Inc. Delivery of a stent at an elevated temperature
US7964210B2 (en) 2006-03-31 2011-06-21 Abbott Cardiovascular Systems Inc. Degradable polymeric implantable medical devices with a continuous phase and discrete phase
US8747878B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device by controlling crystalline structure
US8747879B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device to reduce chance of late inflammatory response
US8596215B2 (en) 2006-05-04 2013-12-03 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8637110B2 (en) 2006-05-04 2014-01-28 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8003156B2 (en) 2006-05-04 2011-08-23 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8465789B2 (en) 2006-05-04 2013-06-18 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8741379B2 (en) 2006-05-04 2014-06-03 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US7761968B2 (en) 2006-05-25 2010-07-27 Advanced Cardiovascular Systems, Inc. Method of crimping a polymeric stent
US7951194B2 (en) 2006-05-26 2011-05-31 Abbott Cardiovascular Sysetms Inc. Bioabsorbable stent with radiopaque coating
US9358325B2 (en) 2006-05-26 2016-06-07 Abbott Cardiovascular Systems Inc. Stents with radiopaque markers
US9038260B2 (en) 2006-05-26 2015-05-26 Abbott Cardiovascular Systems Inc. Stent with radiopaque markers
US9694116B2 (en) 2006-05-26 2017-07-04 Abbott Cardiovascular Systems Inc. Stents with radiopaque markers
US8752267B2 (en) 2006-05-26 2014-06-17 Abbott Cardiovascular Systems Inc. Method of making stents with radiopaque markers
US8752268B2 (en) 2006-05-26 2014-06-17 Abbott Cardiovascular Systems Inc. Method of making stents with radiopaque markers
US8343530B2 (en) 2006-05-30 2013-01-01 Abbott Cardiovascular Systems Inc. Polymer-and polymer blend-bioceramic composite implantable medical devices
US7971333B2 (en) 2006-05-30 2011-07-05 Advanced Cardiovascular Systems, Inc. Manufacturing process for polymetric stents
US20070282434A1 (en) * 2006-05-30 2007-12-06 Yunbing Wang Copolymer-bioceramic composite implantable medical devices
US7959940B2 (en) 2006-05-30 2011-06-14 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical devices
US8034287B2 (en) 2006-06-01 2011-10-11 Abbott Cardiovascular Systems Inc. Radiation sterilization of medical devices
US8486135B2 (en) 2006-06-01 2013-07-16 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from branched polymers
US8603530B2 (en) 2006-06-14 2013-12-10 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8808342B2 (en) 2006-06-14 2014-08-19 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US7731890B2 (en) 2006-06-15 2010-06-08 Advanced Cardiovascular Systems, Inc. Methods of fabricating stents with enhanced fracture toughness
US8048448B2 (en) 2006-06-15 2011-11-01 Abbott Cardiovascular Systems Inc. Nanoshells for drug delivery
US8535372B1 (en) 2006-06-16 2013-09-17 Abbott Cardiovascular Systems Inc. Bioabsorbable stent with prohealing layer
US8925177B2 (en) 2006-06-19 2015-01-06 Abbott Cardiovascular Systems Inc. Methods for improving stent retention on a balloon catheter
US8333000B2 (en) 2006-06-19 2012-12-18 Advanced Cardiovascular Systems, Inc. Methods for improving stent retention on a balloon catheter
US9259341B2 (en) 2006-06-19 2016-02-16 Abbott Cardiovascular Systems Inc. Methods for improving stent retention on a balloon catheter
US9579225B2 (en) 2006-06-19 2017-02-28 Abbott Cardiovascular Systems Inc. Methods for improving stent retention on a balloon catheter
US10342688B2 (en) 2006-06-19 2019-07-09 Abbott Cardiovascular Systems Inc. Methods for improving stent retention on a balloon catheter
US8017237B2 (en) 2006-06-23 2011-09-13 Abbott Cardiovascular Systems, Inc. Nanoshells on polymers
US8592036B2 (en) 2006-06-23 2013-11-26 Abbott Cardiovascular Systems Inc. Nanoshells on polymers
US8293367B2 (en) 2006-06-23 2012-10-23 Advanced Cardiovascular Systems, Inc. Nanoshells on polymers
US9072820B2 (en) 2006-06-26 2015-07-07 Advanced Cardiovascular Systems, Inc. Polymer composite stent with polymer particles
US8128688B2 (en) 2006-06-27 2012-03-06 Abbott Cardiovascular Systems Inc. Carbon coating on an implantable device
US7794776B1 (en) 2006-06-29 2010-09-14 Abbott Cardiovascular Systems Inc. Modification of polymer stents with radiation
US7740791B2 (en) 2006-06-30 2010-06-22 Advanced Cardiovascular Systems, Inc. Method of fabricating a stent with features by blow molding
US7823263B2 (en) 2006-07-11 2010-11-02 Abbott Cardiovascular Systems Inc. Method of removing stent islands from a stent
US7757543B2 (en) 2006-07-13 2010-07-20 Advanced Cardiovascular Systems, Inc. Radio frequency identification monitoring of stents
US7998404B2 (en) 2006-07-13 2011-08-16 Advanced Cardiovascular Systems, Inc. Reduced temperature sterilization of stents
US10145811B2 (en) 2006-07-13 2018-12-04 Abbott Cardiovascular Systems Inc. Radio frequency identification monitoring of stents
US7794495B2 (en) 2006-07-17 2010-09-14 Advanced Cardiovascular Systems, Inc. Controlled degradation of stents
US7886419B2 (en) 2006-07-18 2011-02-15 Advanced Cardiovascular Systems, Inc. Stent crimping apparatus and method
US8016879B2 (en) 2006-08-01 2011-09-13 Abbott Cardiovascular Systems Inc. Drug delivery after biodegradation of the stent scaffolding
US9833342B2 (en) 2006-08-21 2017-12-05 Abbott Cardiovascular Systems Inc. Tracheobronchial implantable medical device and methods of use
US9173733B1 (en) 2006-08-21 2015-11-03 Abbott Cardiovascular Systems Inc. Tracheobronchial implantable medical device and methods of use
US7923022B2 (en) 2006-09-13 2011-04-12 Advanced Cardiovascular Systems, Inc. Degradable polymeric implantable medical devices with continuous phase and discrete phase
US7842737B2 (en) 2006-09-29 2010-11-30 Abbott Cardiovascular Systems Inc. Polymer blend-bioceramic composite implantable medical devices
US8099849B2 (en) 2006-12-13 2012-01-24 Abbott Cardiovascular Systems Inc. Optimizing fracture toughness of polymeric stent
US8262723B2 (en) 2007-04-09 2012-09-11 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from polymer blends with star-block copolymers
US8857118B2 (en) 2007-05-24 2014-10-14 Calera Corporation Hydraulic cements comprising carbonate compound compositions
GB2453304A (en) * 2007-05-24 2009-04-01 Calera Corp Hydraulic cements comprising carbonate compounds compositions
WO2008148055A1 (en) * 2007-05-24 2008-12-04 Calera Corporation Hydraulic cements comprising carbonate compounds compositions
GB2453304B (en) * 2007-05-24 2010-04-21 Calera Corp Hydraulic cements comprising carbonate compound compositions
US20090020044A1 (en) * 2007-05-24 2009-01-22 Constantz Brent R Hydraulic cements comprising carbonate compound compositions
US7906028B2 (en) 2007-05-24 2011-03-15 Calera Corporation Hydraulic cements comprising carbonate compound compositions
US20100132591A1 (en) * 2007-05-24 2010-06-03 Constantz Brent R Hydraulic Cements Comprising Carbonate Compound Compositions
US7735274B2 (en) 2007-05-24 2010-06-15 Calera Corporation Hydraulic cements comprising carbonate compound compositions
US7829008B2 (en) 2007-05-30 2010-11-09 Abbott Cardiovascular Systems Inc. Fabricating a stent from a blow molded tube
US7959857B2 (en) 2007-06-01 2011-06-14 Abbott Cardiovascular Systems Inc. Radiation sterilization of medical devices
US8202528B2 (en) 2007-06-05 2012-06-19 Abbott Cardiovascular Systems Inc. Implantable medical devices with elastomeric block copolymer coatings
US8293260B2 (en) 2007-06-05 2012-10-23 Abbott Cardiovascular Systems Inc. Elastomeric copolymer coatings containing poly (tetramethyl carbonate) for implantable medical devices
US8425591B1 (en) 2007-06-11 2013-04-23 Abbott Cardiovascular Systems Inc. Methods of forming polymer-bioceramic composite medical devices with bioceramic particles
US8048441B2 (en) 2007-06-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Nanobead releasing medical devices
US7901452B2 (en) 2007-06-27 2011-03-08 Abbott Cardiovascular Systems Inc. Method to fabricate a stent having selected morphology to reduce restenosis
US7955381B1 (en) 2007-06-29 2011-06-07 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical device with different types of bioceramic particles
US8821803B2 (en) 2007-08-03 2014-09-02 Errcive, Inc. Porous bodies and methods
US7981375B2 (en) 2007-08-03 2011-07-19 Errcive, Inc. Porous bodies and methods
US8092753B2 (en) 2007-08-03 2012-01-10 Errcive, Inc. Porous bodies and methods
US8097220B2 (en) 2007-08-03 2012-01-17 Errcive, Inc. Porous bodies and methods
US20100298124A1 (en) * 2007-08-03 2010-11-25 Errcive, Inc. Porous Bodies and Methods
US8221694B2 (en) 2007-08-03 2012-07-17 Errcive, Inc. Porous bodies and methods
US8361406B2 (en) 2007-08-03 2013-01-29 Errcive, Inc. Porous bodies and methods
US8361420B2 (en) 2007-08-03 2013-01-29 Errcive, Inc. Porous bodies and methods
US8623287B2 (en) 2007-08-03 2014-01-07 Errcive, Inc. Porous bodies and methods
US8551216B2 (en) 2007-08-03 2013-10-08 Errcive, Inc. Porous bodies and methods
US9138509B2 (en) 2007-09-14 2015-09-22 Musculoskeletal Transplant Foundation Composition for filling bone defects
US20090074871A1 (en) * 2007-09-14 2009-03-19 Musculoskeletal Transplant Foundation Composition for filling bone defects
US10494604B2 (en) 2008-10-31 2019-12-03 DePuy Synthes Products, Inc. Method and device for activating stem cells
US20100119492A1 (en) * 2008-10-31 2010-05-13 Synthes Usa, Llc Method and device for activating stem cells
EP3613845A1 (en) 2008-10-31 2020-02-26 Synthes GmbH Method and device for activating stem cells
US8790707B2 (en) 2008-12-11 2014-07-29 3M Innovative Properties Company Surface-treated calcium phosphate particles suitable for oral care and dental compositions
US8277743B1 (en) 2009-04-08 2012-10-02 Errcive, Inc. Substrate fabrication
US9511345B1 (en) 2009-04-08 2016-12-06 Errcive, Inc. Substrate fabrication
US8679418B2 (en) 2009-04-08 2014-03-25 Errcive, Inc. Substrate fabrication
US8359829B1 (en) 2009-06-25 2013-01-29 Ramberg Charles E Powertrain controls
US9198785B2 (en) 2010-01-30 2015-12-01 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds
US10123894B2 (en) 2010-01-30 2018-11-13 Abbott Cardiovascular Systems Inc. Method of crimping stent on catheter delivery assembly
US11324614B2 (en) 2010-01-30 2022-05-10 Abbott Cardiovascular Systems Inc. Balloon expanded polymer stent
US9867728B2 (en) 2010-01-30 2018-01-16 Abbott Cardiovascular Systems Inc. Method of making a stent
US9827119B2 (en) 2010-01-30 2017-11-28 Abbott Cardiovascular Systems Inc. Polymer scaffolds having a low crossing profile
US9770351B2 (en) 2010-01-30 2017-09-26 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds
US9763818B2 (en) 2010-01-30 2017-09-19 Abbott Cardiovascular Systems Inc. Method of crimping stent on catheter delivery assembly
US11268049B2 (en) 2010-05-20 2022-03-08 Ecolab Usa Inc. Rheology modified low foaming liquid antimicrobial compositions and methods of use thereof
US10563153B2 (en) 2010-05-20 2020-02-18 Ecolab Usa Inc. Rheology modified low foaming liquid antimicrobial compositions and methods of use thereof
US9833932B1 (en) 2010-06-30 2017-12-05 Charles E. Ramberg Layered structures
US10307274B2 (en) 2011-07-29 2019-06-04 Abbott Cardiovascular Systems Inc. Methods for uniform crimping and deployment of a polymer scaffold
US9999527B2 (en) 2015-02-11 2018-06-19 Abbott Cardiovascular Systems Inc. Scaffolds having radiopaque markers
US10531957B2 (en) 2015-05-21 2020-01-14 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
US11596517B2 (en) 2015-05-21 2023-03-07 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
US10610387B2 (en) 2015-06-12 2020-04-07 Abbott Cardiovascular Systems Inc. Scaffolds having a radiopaque marker and methods for attaching a marker to a scaffold
US11478370B2 (en) 2015-06-12 2022-10-25 Abbott Cardiovascular Systems Inc. Scaffolds having a radiopaque marker and methods for attaching a marker to a scaffold

Also Published As

Publication number Publication date
AU746591B2 (en) 2002-05-02
HK1039074B (en) 2003-03-07
AU1154599A (en) 2000-05-08
HK1039074A1 (en) 2002-04-12
DE69810165T2 (en) 2003-07-17
EP1123081A1 (en) 2001-08-16
ATE229350T1 (en) 2002-12-15
JP2002527208A (en) 2002-08-27
DK1123081T3 (en) 2003-03-24
DE69810165D1 (en) 2003-01-23
ZA996601B (en) 2000-10-23
ES2185227T3 (en) 2003-04-16
CA2346651A1 (en) 2000-04-27
WO2000023123A1 (en) 2000-04-27
EP1123081B1 (en) 2002-12-11

Similar Documents

Publication Publication Date Title
US6461632B1 (en) Hardenable ceramic hydraulic cement
US5149368A (en) Resorbable bioactive calcium phosphate cement
Dorozhkin Calcium orthophosphate cements for biomedical application
US6224635B1 (en) Implantation of surgical implants with calcium sulfate
ES2252254T3 (en) A COMPOSITION FOR AN INJECTABLE OSEO MINERAL SUBSTITUTE MATERIAL.
ES2330108T3 (en) A NEW COMPOSTION OF BONE SUBSTITUTE.
US7758693B2 (en) Strontium-apatite cement preparations, cements formed therefrom, and uses thereof
Pietrzak et al. Calcium sulfate bone void filler: a review and a look ahead
US5296026A (en) Phosphate glass cement
ES2260616T3 (en) HYDRAULIC CEMENT BASED WITH CALCIUM PHOSPHATE BASED FOR SURGICAL USE.
EP2266634B1 (en) Rapid-hardening calcium phosphate cement compositions
CN100396641C (en) Mganesium-ammonium-phosphate cement, prodn. of same and use
CN102580144B (en) Surgical calcium phosphate citrate-containing cement and method of manufacturing same
ES2304515T3 (en) PREPARED FOR CEMENT OF APTRICT OF STRONTIUM AND ITS USES.
JP5039542B2 (en) Injectable cement compositions useful as bone substitutes
JP2003507090A (en) Compositions for Transplantation into Human and Animal Body
US8784551B2 (en) Bone cement formula and bioresorbable hardened bone cement composites prepared with the same
EP2353619A1 (en) Preparation of Bone Cement Compositions
US9180137B2 (en) Preparation of bone cement compositions
EP2450064B1 (en) Bone Cement Formula and Bioresorbable Hardened Bone Cement Composites Prepared with the Same
Dorozhkin Self-Setting Formulations Calcium Orthophosphate (CaPO4)
WO2024133597A1 (en) Bioadhesive composition
WO2012054010A1 (en) Bone cement formula and bioresorbable hardened bone cement composites prepared with the same

Legal Events

Date Code Title Description
AS Assignment

Owner name: SYNTHES (U.S.A.), PENNSYLVANIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GOGOLEWSKI, SYLWESTER;REEL/FRAME:011747/0374

Effective date: 20010206

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362

FP Lapsed due to failure to pay maintenance fee

Effective date: 20061008